RT Journal Article
SR Electronic
T1 Inhibition of granulocyte ROS production by opioids prevents regeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 182584
DO 10.1101/182584
A1 Elodie Labit
A1 Lise Rabiller
A1 Christophe Guissard
A1 Mireille Andre
A1 Christine Rampon
A1 Corinne Barreau
A1 Béatrice Cousin
A1 Audrey Carriere
A1 Margaux Raffin
A1 Gilles Mithieux
A1 Mohamad Ala Eddine
A1 Bernard Pipy
A1 Anne Lorsignol
A1 Sophie Vriz
A1 Cecile Dromard
A1 Louis Casteilla
YR 2017
UL http://biorxiv.org/content/early/2017/08/30/182584.abstract
AB Inhibition of regeneration and induction of healing are classic outcomes of tissue repair in adult mammals. Here, by using gain and loss of function experiments, we demonstrate that both endogenous and exogenous opioids prevent tissue regeneration in adults, by inhibiting the early reactive oxygen species (ROS) production occurring after lesion and required for regeneration. These effects can be overcome and regeneration induced by the use of an opioid antagonist. These results, obtained in both gold-standard adult zebrafish and a newly-developed model of regeneration in adult mammals, demonstrate that this mechanism can be considered as a general paradigm in vertebrates. In addition, we show that opioids act via signaling through peripheral mu-receptors expressed on granulocytes. This work clearly demonstrates the deleterious role of opioids on tissue regeneration through the control of ROS production in vertebrates and thus questions about opioid-based analgesia in perioperative care.